ABSTRACT (Overall Core) This proposal is to establish in New Mexico an exploratory Alzheimer's Disease Research Center (NM eADRC). The Center goals are: 1) to build infrastructure and hire faculty to enhance Alzheimer's disease (AD) research; 2) to meet the needs of rural communities with health disparities, and 3) to use multimodal biomarkers, including CSF and MRI, to incorporate vascular disease into the new NIA-AA Alzheimer's disease (AD) biological definition, improving patient stratefication. This P20 NM eADRC will build toward the P30 ADRC. We plan to hire new faculty with expertise in Alzheimer's disease (AD) and related dementias (RD). Infrastructure needs for care of the elderly will be met by the construction of new 7 million dollar building that will house three centers: Movement disorders, Geriatrics, and Center for Memory and Aging, creating synergy in care of the elderly. The NM eADRC will address the unmet needs in dementia care related to disparities, particularly in the large American Indian (AI) population. There are challenges to improving dementia care to AI that include cultural insensitivity, low income and educational levels, and long distances to travel for specialist care. We will overcome these barriers by using community health representatives to perform cognitive screening and a program for mobile on-site screening and testing (MOSST) that includes neuropsychological testing and mobile 1.5T MRI for imaging. This will fill a gap in the national AD databases for data on minorities. Vascular disease is a major co-morbidity with AD that accelerates the cognitive decline. It is estimated that up to 70% of nongenetic AD is mixed dementia (MX), making this an important group to identify prior to autopsy. We have developed biomarkers that can successfully stratify patients. This involves the use of CSF and MRI studies, and allows for the addition of the vascular feature (V) to the amyloid (A), tau (T), and neurodegeneration (N) components of the NIA-AA formula for diagnosis of AD. Biomarkers in the CSF have been identified by the MarkVCID consortium that indicate inflammation, which occurs when both AD and vascular disease are present. The NM eADRC will measure these unique biomarkers in the newly recruited participants, and provide these services to other ADRCs that are interested. The blood- brain barrier (BBB) has been implicated in the pathophysiology of AD. We plan to measure BBB permeability in gray and white matter in patients with AD and RD along with VCID and MX to better understand its role in dementia. The NM eADRC will be nidus for AD research to a large community of researchers around the state and will be major center within the Medical School Administrative structure. With the ability to bring in new faculty, build new buildings, and bring together the community of scientists interested in dementia in NM, it will make a huge impact that will provide the infrastructure for a successful P30 Center application.